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When a person experiencing a period of mania related to bipolar disorder improves following treatment with a combination of a mood stabilizer and an atypical antipsychotic, the standard of practice is to continue both medications in order to maintain the improvement and prevent future mood episodes.

However, antipsychotic medication can cause many serious side effects, including weight gain and metabolic syndrome (increased blood pressure, a high blood sugar level, excess abdominal weight gain, and abnormal cholesterol levels), heightening the risk of cardiovascular disease. For this reason, physicians agree that antipsychotic therapy should only be prescribed long-term if the benefits of using the medication outweigh the risks.

“While antipsychotic adjunctive therapy is beneficial to prevent relapse of mood episodes, the optimal duration of such therapy was unknown,” says Dr. Lakshmi Yatham, clinician-scientist at the Djavad Mowafaghian Centre for Brain Health and Regional Head of Psychiatry and Regional Program Medical Director at Vancouver Coastal Health and Providence Health Care. Dr. Yatham’s team at UBC sought to address this question by conducting a multi-center study in bipolar patients who recently remitted from a manic episode following treatment with a combination of a mood stabilizer and an atypical antipsychotic (i.e., risperidone or olanzapine).

Study participants were assigned at random to one of three conditions: discontinuation of antipsychotic medication and substitution with placebo at the beginning of the trial (0-week group) or 24 weeks after enrolment in the study, or continuation of the antipsychotic therapy throughout the 52-week trial.

The researchers found that patients on antipsychotics and mood stabilizers for 24 weeks following remission of their manic episode had about half the risk of relapse as patients who tapered off antipsychotics following remission (the 0-week group).

However, the benefits of continuing antipsychotics beyond 24 weeks were not apparent as the mood episode relapse rates were no different between the 24 and 52 weeks groups.

Futhermore, the weight gain was significantly greater in the 52 weeks group. The 24-week group gained an average of 0.1 kilograms while the 52-week group gained an average of 3.2 kilograms; the 0-week group lost 0.2 kilograms on average.

"This study has immediate practical implications for long term treatment of bipolar disorder," says Dr. Yatham. "The optimal duration of atypical antipsychotic adjunctive therapy likely is 24 weeks for the vast majority of bipolar patients."